title: Mutation and protein expression analysis of CYP1A1 gene-a study on female breast cancer cases from India.
abstract: Increased risk may be associated with exposure to genotoxic agents during breast development because the undifferentiated ductal elements of breast are more susceptible to the action of genotoxic early in life and thus an impairment in Cytochrome P 4501A1 (CYP1A1) may contribute to the development of breast cancer. Therefore, we carried out the population-based study in a total of 105 Indian female breast cancer cases with equal normal adjacent controls. A total of 20 samples (20/105, 19.04 %) showed final mutations in the exon 7 of the CYP1A1 gene where 5 cases harbored frame shift mutation (deletion of G nucleotide), and the remaining were missense mutation observed in 15 cases of breast cancer with significant association to histological grade (chi square -7.20, p = 0.02), tumor stage (chi square -6.36, p = 0.01), menopausal stage (chi square -9.76, p = 0.001), and ER status (chi square -4.22, p = 0.03). We further did protein expression analysis of CYP1A1 through immunohistochemistry where 66 cases showed down or no expression (+) (66/105, 62.85 %), 28 cases with moderate expression (++) (28/105, 26.66 %), and 11 cases with high expression (+++) (11/105, 10.47 %). Highly significant associations were observed between protein expression and clinico-pathological variables like Her 2 category (chi square = 31.73, p < 0.0001) and tumor stage (chi square = 10.27, p = 0.005). Importantly, mutation(s) of the type like deletion of A nucleotide and missense mutation (Gly > Val) exclusively showed low (+) or no expression for the CYP1A1 protein when studied in relation to each other. In summary, CYP1A1 may be associated with breast cancer and its down regulation may serve as an important tool in the field of biomarker study.
authors.affiliation: Department of Biochemistry, Jamia Hamdard, New Delhi, India.
authors.forename: Mohammad Zeeshan
authors.initials: MZ
authors.lastname: Najm
authors.forename: Salman
authors.initials: S
authors.lastname: Akhtar
authors.forename: Istaq
authors.initials: I
authors.lastname: Ahmad
authors.forename: Shilpi
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Nasar
authors.initials: N
authors.lastname: Mallick
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Shuaib
authors.initials: S
authors.lastname: Zaidi
authors.forename: Waseem Ahmad
authors.initials: WA
authors.lastname: Siddiqui
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1